β-catenin is a subunit of the cadherin protein complex. β-catenin is critically required for cell adhesion and as an intracellular mediator of the Wnt pathway. The Wnt signaling pathway plays critical roles in embryonic development and tumorigenesis. A smaller pool of β-catenin in the nucleus and cytoplasm is regulated by Wnt signals. The Wnt signaling activates gene transcription through forming a complex between DNA-binding high monility group (HMG)-box proteins of the Tcf/LEF family and β-catenin. In unstimulated cells, cytosolic β-catenin is constitutively degraded by a ubiquitin ligase-proteosome system. Wnt signaling inhibits this process, allowing β-catenin to accumulate and subsequently translocate to the nucleus where it forms a transcriptional activating complex with members of the TCF/LEF-1 family of transcription factors. Tcf/LEF-1 proteins by themselves have no innate transcriptional activity and they repress transcription of Wnt target genes by recruiting corepressors to the promoter. Transcriptional activation of target genes occurs when β-catenin binds the Tcf/LEF-1 factors and recruits transcription factors, such as p300/CBP and the TATA binding protein, to the promoter (Hecht, A. et. al. J. Biol. Chem. 274 (1999), pp. 18017-18025). Genetic and biochemical studies have demonstrated that the Wnt signaling pathway controls many processes in embryonic development in both vertebrates and invertebrates. Inappropriate activation of the Wnt intracellular pathway is associated with various human cancers, in particular colon cancer (K. W. Kinzler and B. Vogelstein, Cell 87 (1996), pp. 159-170). Key molecular lesions in colorectal, hepatocellular carcinoma (HCC), and other cancers are caused by β-catenin-dependent transactivation of T cell factor (TCF)-dependent genes, for example, c-myc, cyclin D1, VEGF, and others. For tumorigenesis, formation of the complex between β-catenin and TCF is the critical step in the activation of Wnt target genes (M. Bienz and H. Clevers Cell 103 (2000), pp. 311 -320). Mutations in the Adenomatous polyposis coli (APC) gene, a key regulator of cellular β-catenin levels, are found in most colorectal cancers. Targeting elements downstream of APC in the Wnt pathway, such as formation and activity of the Tcf4-β-catenin protein complex represents a potentially powerful means of treating common human cancers, and there is a strong need for therapeutic approaches targeting components of the Wnt signaling pathway such as the Tcf4-β-catenin complex.